Skin transplants are often required in connection with many injuries and also in connection with surgical operations, but suitable skin from the injured themselves or others is not always available. It has therefore been attempted for a long time to cover particularly large wound areas, such as burn injuries, with other materials in order to prevent the loss of fluids and external infections. Experiments in this field have been performed for some years with "artificial skin" on the basis of collagen fibers. The results obtained with such a type of "artificial skin" have been mixed so far.
The long-fiber, linear-colloid, scleroproteins of the extracellular matrix which, together with proteoglycan, appear in connective tissue, in the protein-containing basic substance of bones and in dentine, are called collagen. Depending on their origin, the composition of the proteins can vary, various types of collagens are known which, however, not all have a fiber structure. The small proportion of tryptophan, tyrosin and cystine in collagens is remarkable, but collagens are distinguished by a large proportion of glycine, prolin and in particular 4-hydroxy-prolin. Collagens are first synthesized in fibroblasts, i.e. cells of the connective tissue, in the form of procollagen chains of a molecular weight of approximately 140,000. Hydroxylation of prolin and lysine under the influence of ascorbic acid and glycolization only take place in the chain, after which three chains then combine in the form of levo-rotated helices which in turn are dextroverted around each other. This substance then is excreted in the extracellular space, in which peptides are split off the ends of the chains, so that so-called tropocollagen is created, which combines into fibrils. While the tropocollagen is still salt- or acid-soluble, collagen fibrils are insoluble. The tropocollagen of a molecular weight of approximately 300,000 consists of three polypeptide chains which may have a slightly different amino acid sequence. As a rule, two chains are identical, the third has a different structure.
In contrast to most proteins of the human or animal body, collagens are not continuously renewed, instead they have a long biological half-life which may be up to 300 days. The collagens are quite resistant to enzymatic decomposition, essentially, the enzymatic decomposition of native collagens can only be achieved by means of collagenase. The soluble fission products being created following the proteolysis of the collagen fibrils are hydrolized by other proteases into peptides and amino acids.
Soluble as well as insoluble collagens have already been experimentally used as "artificial skin". Corresponding products have been described, for example, in Japanese Patent Application 59 160464 or in U.S. Pat. No. 4,600,533. The material has also been suggested for endoprotheses, for example the European Patent Application 85 200045. An "artificial skin" of this type reduces fluid loss and protects against external infection, in addition, this type of artificial skin is intended to have an inflammation-reducing and hemostatic effect and to increase the growth of epithelic cells. The collagens used as the raw material up to now are soluble collagens as a rule because of easier processing. This has the disadvantage that the membranes or films have relatively only little stability because they consist of non-fibrous collagens which to not natively occur in this form. In addition, the collagen used continues to be enzymatically dissolved. Up to now, these membranes or films were made of collagen gels, which were produced in accordance with various techniques, known per se, and were then converted into solid form. Corresponding products are described, for example, in U.S. Pat. Nos. 4,600,533, 4,689,399 or 4,725,641 and 4,294,241. In accordance with U.S. Pat. No. 3,800,792, an attempt was made to improve the lack of stability in that the sponge structure produced from a collagen gel was linked and provided with a plastic film, however, this clearly worsened the adaptation and adherence of the material to the wound. The fact that, as already mentioned, the adherence of these films to the wound is not very pronounced when used as a dressing, is a disadvantage of all collagen films known up to now, so that as a rule additional fixation of the edges is required, particularly, if large areas must be covered. A further difficulty with the materials known up to now consists in that they can be decomposed relatively quickly and that, as a result of their processing, they still have a considerable proteoglycan content, which can lead to allergic reactions which as a rule are slight, but may be markedly pronounced in individual cases, because this is, after all, a material which is alien to the body and not human. In addition, it is not very easy to maintain products made of soluble collagen sterile and to make them capable of storage, because the decomposition or further decomposition of the amino acid chains cannot be completely disrupted. When producing films or membranes of insoluble collagen, however, there is always the difficulty of cleaning the fibers of extraneous material, such as the allergy-creating proteoglycans, to the extent that a quite safe use, in particular on large areas of the body, is possible. A combination of a collagen film of soluble collagen with hyaluronic acid is already known from Japanese Patent Application 61 041462. Hyaluronic acid comprises the basic components of D-glycuronic acid and N-acetyl-D-glucosamine in a 1,3-glycosidic bond and can have molecular weights between approximately 50,000 and several million, depending on its origin and processing. Hyaluronic acid can bond to fibrins and together with them forms a three-dimensional matrix, by means of which the original fibrin matrix is deformed, swells and becomes porous. Faster and improved infiltration and migration of cells into the matrix is made possible because of this. Hyaluronic acid has an intense stimulating effect on the speed of formation of fibrin matrices which were induced by thrombin. Thus the hyaluronic acid content in the wound increases shortly after the injury and, in addition to cell infiltration and swelling of the matrix, the substance also affects the phagocytosis and vascularization of newly formed tissue. Therefore hyaluronic acid plays a very essentiar role in the building, conversion and decomposition of the fibrin matrix, so that its addition to collagen films is desirable, because the hyaluronic acid ensures faster healing of the wound with less complications.
However, the "artificial skins on a collagen basis" known up to now still have the disadvantages of not displaying good adherence, being able to trigger immune reactions and allergies and not being particularly inexpensive. In addition, the permeability to water -is great and the decomposition too fast. Therefore there is still a need for further wound covering materials on the basis of collagen fibers which do not have these disadvantages.